System and method for programmably controlling electrode activation sequence in a multi-site cardiac stimulation device

ABSTRACT

An implantable multi-chamber cardiac stimulation device includes flexibly programmable electrode sensing configurations, and is capable of precisely controlling the stimulation sequence between multiple sites. The stimulation device provides a plurality of connection ports that allow independent connection of each electrical lead associated with a particular stimulation site in the heart. Each connection port further provides a unique terminal for making electrical contact with only one electrode such that no two electrodes are required to be electrically coupled. Furthermore, each electrode, whether residing on a unipolar, bipolar or multipolar lead, may be selectively connected or disconnected through programmable switching circuitry that determines the electrode configurations to be used for sensing and for stimulating at each stimulation site. The stimulation device possesses unique sensing and output configurations associated with each stimulation site, such that depolarizations occurring at each stimulation site can be detected independently of events occurring at other sites within the heart, and such that each site can be stimulated independently of other sites or on a precisely timed basis triggered by events occurring at other sites. The stimulation device is further capable of uniquely programming coupling intervals for precisely controlling the activation sequence of stimulated sites. Coupling intervals are selected so as to provide optimal hemodynamic benefit to the patient.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a division of copending U.S. application Ser.No. 09/835,006, filed Apr. 12, 2001, titled “System and Method forAutomatically Selecting Electrode Polarity During Sensing andStimulation.”

FIELD OF THE INVENTION

[0002] This invention relates generally to programmable cardiacstimulating devices. More specifically, the present invention isdirected to an implantable stimulation device and associated method forcontrolling the electrode sensing and stimulation configurations and theactivation sequence in a multi-chamber cardiac stimulation device usingnoninvasive programming techniques.

BACKGROUND OF THE INVENTION

[0003] In a normal human heart, the sinus node, generally located nearthe junction of the superior vena cava and the right atrium, constitutesthe primary natural pacemaker initiating rhythmic electrical excitationof the heart chambers. The cardiac impulse arising from the sinus nodeis transmitted to the two atrial chambers, causing a depolarizationknown as a P-wave and the resulting atrial chamber contractions. Theexcitation pulse is further transmitted to and through the ventriclesvia the atrioventricular (A-V) node and a ventricular conduction systemcausing a depolarization known as an R-wave and the resultingventricular chamber contractions.

[0004] Disruption of this natural pacemaking and conduction system as aresult of aging or disease can be successfully treated by artificialcardiac pacing using implantable cardiac stimulation devices, includingpacemakers and implantable defibrillators, which deliver rhythmicelectrical pulses or other anti-arrhythmia therapies to the heart at adesired energy and rate. One or more heart chambers may be electricallystimulated depending on the location and severity of the conductiondisorder.

[0005] Cardiac pacemakers conventionally stimulate a heart chamber byapplying current pulses to cardiac tissues via two electrodes, a cathodeand an anode. Standard pacing leads are available in either of twoconfigurations, unipolar leads or bipolar leads, depending on thearrangement of the electrodes of a particular lead. A unipolar pacinglead contains a single electrode, normally the cathode, which extendspervenously distal from the pacemaker in an insulating enclosure untilit is adjacent to the tip of the lead where the insulation is terminatedto provide for electrical contact of the cathode with the heart tissue.The anode provides a return path for the pacing electrical circuit. Fora unipolar lead, the anode is the pacemaker case.

[0006] A bipolar lead contains two electrodes within an insulatingsheath, an anode that extends distal from the pacemaker to a positionadjacent to, but spaced from, the electrode tip, and a cathode that alsoextends distal from the pacemaker, but terminates a short distancedistal of the anode, at the lead tip. The anode commonly takes the formof a ring having greater surface area than the cathode tip. Aninsulating barrier separates the cathode and anode of a bipolar lead. Inpresent-day pacemakers, circuits for pacing and sensing, which determinetip, ring and case electrode connections, are provided. Thus, thepacemakers can be programmed via telemetry for either bipolar orunipolar operation with respect to either sensing or pacing operations.

[0007] A single-chamber pacemaker delivers pacing pulses to one chamberof the heart, either one atrium or one ventricle, via either a unipolaror bipolar electrode. Single-chamber pacemakers can operate in either atriggered mode or a demand mode. In a triggered mode, a stimulationpulse is delivered to the desired heart chamber at the end of a definedtime-out interval to cause depolarization of the heart tissue(myocardium) and it's contraction. The stimulating pulse must be ofsufficient energy to cause depolarization of the heart chamber, acondition known as “capture.” The lowest pulse energy required toachieve capture is termed “threshold.” The pacemaker also delivers astimulation pulse in response to a sensed event arising from thatchamber when operating in a triggered mode.

[0008] When operating in a demand mode, sensing and detection circuitryallow for the pacemaker to detect if an intrinsic cardiacdepolarization, either an R-wave or a P-wave, has occurred within thedefined time-out interval. If an intrinsic depolarization is notdetected, a pacing pulse is delivered at the end of the time-outinterval. However, if an intrinsic depolarization is detected, thepacing pulse output is inhibited to allow the natural heart rhythm topreside. The difference between a triggered and demand mode of operationis the response of the pacemaker to a detected native event.

[0009] Dual chamber pacemakers are now commonly available and canprovide either trigger or demand type pacing in both an atrial chamberand a ventricular chamber, typically the right atrium and the rightventricle. Both unipolar or bipolar dual chamber pacemakers exist inwhich a unipolar or bipolar lead extends from an atrial channel of thedual chamber device to the desired atrium (e.g. the right atrium), and aseparate unipolar or bipolar lead extends from a ventricular channel tothe corresponding ventricle (e.g. the right ventricle). In dual chamber,demand-type pacemakers, commonly referred to as DDD pacemakers, eachatrial and ventricular channel includes a sense amplifier to detectcardiac activity in the respective chamber and an output circuit fordelivering stimulation pulses to the respective chamber.

[0010] If an intrinsic atrial depolarization signal (a P-wave) is notdetected by the atrial channel, a stimulating pulse will be delivered todepolarize the atrium and cause contraction. Following either a detectedP-wave or an atrial pacing pulse, the ventricular channel attempts todetect a depolarization signal in the ventricle, known as an R-wave. Ifno R-wave is detected within a defined atrial-ventricular interval (AVinterval or delay), a stimulation pulse is delivered to the ventricle tocause ventricular contraction. In this way, rhythmic dual chamber pacingis achieved by coordinating the delivery of ventricular output inresponse to a sensed or paced atrial event.

[0011] Mounting clinical evidence supports the evolution of more complexcardiac stimulating devices capable of stimulating three or even allfour heart chambers to stabilize arrhythmias or to re-synchronize heartchamber contractions (Ref: Cazeau S. et al., “Four chamber pacing indilated cardiomyopathy,” Pacing Clin. Electrophsyiol 1994 17(11 Pt2):1974-9). Stimulation of multiple sites within a heart chamber hasalso been found effective in controlling arrhythmogenic depolarizations(Ref: Ramdat-Misier A., et al., “Multisite or alternate site pacing forthe prevention of atrial fibrillation,” Am. J. Cardiol., 1999 11;83(5b):237D-240D).

[0012] In order to achieve multi-chamber or multi-site stimulation in aclinical setting, conventional dual-chamber pacemakers have now beenused in conjunction with adapters that couple together two leads goingto different pacing sites or heart chambers. Reference is made to U.S.Pat. No. 5,514,161 to Limousin in which a triple chamber cardiacpacemaker, with the right and left atrial combined with a rightventricular lead, is described. Cazeau et al. (Pacing Clin.Electrophsyiol 1994 17(11 Pt 2):1974-9) describe a four chamber pacingsystem in which unipolar right and left atrial leads are connected via abifurcated bipolar adapter to the atrial port of a bipolar dual chamberpacemaker. Likewise, unipolar right and left ventricular leads areconnected via a bifurcated bipolar adapter to the ventricular channel.The left chamber leads were connected to the anode terminals and theright chamber leads were connected to the cathode terminals of the dualchamber device. In this way, simultaneous bi-atrial or simultaneousbi-ventricular pacing is achieved via bipolar stimulation but withseveral limitations.

[0013] Firstly, this configuration of bipolar stimulation is distinctlydifferent from a conventional bipolar lead configuration wherein boththe cathode and anode are located a short distance apart, approximatelyone centimeter, on the same lead. In the bi-chamber pacing configurationdescribed above, the anode and cathode are in fact located on twodifferent leads positioned in two different locations, severalcentimeters apart. In addition, since the tip electrode of one lead isforced to be the anode, and this has a significantly smaller surfacearea than the anode of a classic bipolar lead, the relative resistanceor impedance is higher with this lead system. In such a bipolar,bi-chamber pacing configuration, the threshold energy is likely to berelatively higher than in conventional bipolar stimulation in partbecause of the higher impedance of the electrode system. In addition,the electrode used for stimulation in the left heart chamber is usuallywithin the coronary sinus or a cardiac vein, not making direct contactwith the myocardium. As such, the energy needed to accommodatebi-chamber stimulation will usually be higher than that which iscommonly required for single chamber stimulation using bipolar leads.

[0014] A potential risk that exists when higher output settings areused, as may be needed to ensure bi-chamber stimulation, iscross-chamber capture, also known as cross-stimulation (Ref: Levine P A,et al., Cross-stimulation: the unexpected stimulation of the unpacedchamber, PACE 1985: 8: 600-606). If bi-atrial stimulation is deliveredin a bipolar configuration across one electrode located in the rightatrium and another electrode located in the left atrium, which inactuality is the coronary sinus which lies between the left atrium andleft ventricle, the stimulation energy could conceivably be high enoughto inadvertently capture one or both ventricles simultaneously. Suchcross-chamber capture is a highly undesirable situation in that theupper and lower chambers would contract against each other causingsevere cardiac output perturbation. This is also likely to occur withbipolar bi-ventricular stimulation with respect to cross-stimulation ofthe atrial chambers if the left ventricular lead located within acardiac vein is in close anatomic proximity to the left atrium and highoutputs are required to assure capture.

[0015] Another limitation of the multi-chamber stimulation systemsdescribed above is that simultaneous stimulation of left and rightchambers, as required when two leads are coupled together by oneadapter, is not always necessary nor desirable. For example, in somepatients conduction between the two atria may be compromised, howeverthe pacemaking function of the sinus node in the right atrium may stillbe normal. Hence, detection of an intrinsic depolarization in the rightatrium could be used to trigger delivery of a pacing pulse in the leftatrium. Since an intrinsic depolarization has occurred in one chamber,simultaneous stimulation of both chambers in this situation isunnecessary.

[0016] In another example, when inter-atrial or inter-ventricularconduction is intact, stimulation in one chamber may be conductednaturally to depolarize the second chamber. A stimulation pulsedelivered in one chamber, using the minimum energy required todepolarize that chamber, will be conducted to the opposing chamber thusdepolarizing both chambers. In this case, stimulation of both chamberssimultaneously would be wasteful of battery energy.

[0017] Another limitation is that, in the presence of an inter-atrial orinter-ventricular conduction defect, one may want to control theinterval between a sensed or paced event in one chamber and delivery ofa stimulation pulse to the other chamber. If pacing is required in bothchambers, the control of the sequence of the stimulation pulse deliveryto each chamber, rather than the simultaneous delivery of stimulationpulses, may be desirable in order to achieve a specific activationsequence that has hemodynamic benefit.

[0018] Yet another limitation is that, once implanted, the designationof cathode and anode assignments is fixed and cannot be reassigned inorder to determine the polarity that results in the lowest stimulationthresholds, to achieve a desired directionality of the stimulationdelivery or to obtain the optimal sequencing of stimulation and/orsensing to optimize hemodynamic function. Typically, the electrode inthe right chamber is connected to the cathode terminal and the electrodein the left chamber is connected to the anode terminal. In other cases,the electrode in the left chamber is connected to the cathode terminalwhile the right chamber electrode is connected to the anode. In somepatients, a lower stimulation threshold or an improved excitationpattern or perhaps even hemodynamic benefit might be achieved byreversing the cathode and anode locations yet this cannot be donewithout operative intervention.

[0019] In the first generation of multi-chamber devices, an adapter wasrequired to connect multiple leads to a conventional dual chamberdevice, a requirement that adds cost and time to the implant procedure.Adapters can be cumbersome and an additional site for potential leadbreakage or discontinuity, essentially adding bulk and a “weak link” tothe implanted system. In certain current devices, adapters are no longerrequired. The connection between leads is hardwired internally in theconnector block coupling the ventricular leads to the ventricularchannel and the atrial leads to the atrial channel. While this designadvantageously eliminates the need for adapters, the hardwireconnections preclude the potential to non-invasively adjust the polarityorientation. This also prevents introducing separate timing betweenstimulation pulses delivered to each chamber or responding with anyprogrammable delays to a sensed event by delivery of an output pulse tothe other chamber.

[0020] To address some of these limitations, Verboven-Nelissen proposesa method and apparatus that includes a multiple-chamber electrodearrangement having at least two electrodes placed to sense and/or pacedifferent chambers or areas of the heart. Reference is made to U.S. Pat.No. 5,720,518. The proposed method involves switching from a bipolar toa unipolar configuration during sensing for determining the originationsite of a detected depolarization signal. If the signal is determined tohave arisen from the SA node in the right atrium, a conduction intervalis applied to allow the cardiac signal to properly propagate to theother heart chambers. If no cardiac signal is detected in anothercardiac chamber, for example, the left atrium, then pacing is initiatedin that chamber at the end of the conduction interval. In this example,the interval is equal to the inter-atrial conduction time (i.e. the timerequired for a P-wave cardiac signal to propagate from right atrium toleft atrium). However the inter-atrial conduction time may vary overtime and the time for an excitation pulse to propagate from the rightchamber to the left chamber may be different than the propagation timefrom the left chamber to the right chamber. In addition, the conductiontime from the right atrium to the left atrium may vary from thatrequired to go from the left atrium to the right atrium. Depending onthe site of origin of the detected depolarization, it may behemodynamically beneficial to control the coupling interval between thedetected depolarization and the triggered output to the other chamber.U.S. Pat. No. 5,720,518 does not address the ability to control theinterval between detection and stimulation within the atria orventricles in the setting of multisite stimulation.

[0021] Reference is also made to U.S. Pat. No. 5,902,324 to Thompson etal. in which a multi-channel pacing system having two, three or fourpacing channels, each including a sense amplifier and pace output pulsegenerator, is described. A pacing pulse or detection of a spontaneousdepolarization in one of the right or left heart chambers is followed bya short conduction delay window. A pacing pulse that would otherwise bedelivered at the termination of the conduction delay window in theopposing heart chamber is inhibited if the conducted depolarization waveis sensed within the conduction delay window. While the duration of theconduction delay window can be programmed, no method is provided bywhich to select the optimal interval between chamber depolarizations.

[0022] Patients with marked hemodynamic abnormalities may benefit frommulti-site or multi-chamber pacing that controls the activation sequenceof the heart chambers. Precise control of the activation sequence mayimprove the coordination of heart chamber contractions resulting in moreeffective filling and ejection of blood from the heart. Patients withhemodynamic abnormalities often have conduction defects due to dilationof the heart or other causes. Yet, even in patients with intactconduction, precise control of the timing and synchronicity of heartchamber contractions may provide hemodynamic benefit.

[0023] There remains an unmet need, therefore, for a multi-chamber ormulti-site cardiac stimulation device that allows independentstimulation and sensing at multiple sites within the heart as well asflexible selection of stimulation sequence and timing intervals betweenthese stimulation sites. It would thus be desirable to provide amultisite or multichamber cardiac stimulation device having independentsensing and output circuitry for each pacing site. It would further bedesirable to allow flexible selection of sensing and stimulationpolarity for each stimulation site, including the designation of cathodeand anode assignment during bichamber stimulation. Further, it would bedesirable to provide flexible programming of the stimulation sequenceand timing intervals associated with multisite or multichamber pacing.Different timing intervals should be advantageously selectable dependingon the origination site of a detected depolarization wave or a desireddirectionality of depolarization in order to achieve optimal hemodynamicor electrophysiological benefit for the patient.

SUMMARY OF THE INVENTION

[0024] The present invention addresses this need by providing animplantable multichamber or multisite cardiac stimulation device inwhich the electrode configurations for sensing and stimulation areflexibly programmable, and the stimulation sequence between multiplesites can be precisely controlled.

[0025] One aspect of the present invention is to provide a plurality ofconnection ports, preferably two through four connection ports, thatallow independent connection to the stimulation device of eachelectrical lead associated with a particular stimulation site in theheart. Each connection port further provides a unique terminal formaking electrical contact with only one electrode such that no twoelectrodes are required to be electrically coupled. Furthermore, eachelectrode, whether residing on a unipolar, bipolar or multipolar lead,may be selectively connected or disconnected through programmableswitching circuitry that determines the electrode configurations to beused for sensing and for stimulating at each stimulation site.

[0026] Another aspect of the present invention is a unique sensingcircuit associated with each stimulation site such that depolarizationsoccurring at each stimulation site can be detected independently ofevents occurring at other sites within the heart. This independentsensing advantageously allows the location of a detected depolarizationto be recognized by the stimulation device. The desired electrodes to beused for sensing in a specific heart chamber or at a specific sitewithin a heart chamber are connected to the input of the sensing circuitvia programmable switching circuitry.

[0027] Still another aspect of the present invention is a unique outputcircuit associated with each stimulation site such that each site can bestimulated independently of other sites or on a precisely timed basistriggered by events occurring at other sites. The electrodes used forstimulation at a specific site may be different than those used forsensing at the same site.

[0028] Yet another aspect of the present invention is the ability toprogram unique coupling intervals for precisely controlling theactivation sequence of stimulated sites. Coupling intervals may bedefined in relation to the originating location of a detecteddepolarization or in relation to stimulus delivery at another location.Coupling intervals are advantageously selected in a way that providesoptimal hemodynamic benefit to the patient by overcoming variousconduction disorders or improving coordination of heart chambers inpatients suffering from heart failure. One embodiment of the presentinvention includes a method for automatically determining the optimalcoupling intervals and adjusting the programmed settings based onmeasurements related to the hemodynamic state of the heart.

BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Further features and advantages of the present invention may bemore readily understood by reference to the following description takenin conjunction with the accompanying drawings, in which:

[0030]FIG. 1 is a simplified, partly cutaway view illustrating animplantable stimulation device in electrical communication with at leastthree leads implanted into a patient's heart for deliveringmulti-chamber stimulation and shock therapy;

[0031]FIG. 2 is a functional block diagram of the multi-chamberimplantable stimulation device of FIG. 1, illustrating the basicelements that provide pacing stimulation, cardioversion, anddefibrillation in four chambers of the heart;

[0032]FIG. 3 is a simplified, partly cutaway view illustrating animplantable stimulation device in electrical communication with at leastfour bipolar leads implanted into a patient's heart representing apreferred embodiment of the present invention;

[0033]FIG. 4 is a block diagram of the stimulation device of FIG. 3,illustrating a switch with four ports for connection to four leads;

[0034]FIG. 5 depicts a flow chart describing an overview of a method forautomatically configuring sensing electrodes for use in the cardiacstimulation device of the present invention;

[0035]FIGS. 6 through 9 depict flow chart describing a method forautomatically configuring stimulation electrodes for use in the cardiacstimulation device of the present invention; and

[0036]FIG. 10 is a flow chart describing an overview of a methodimplemented by the stimulation device of FIG. 2, for automaticallyadjusting the coupling intervals used in the methods of FIGS. 5 - 9, toachieve an optimal physiological response to a multichamber stimulationtherapy.

DETAILED DESCRIPTION OF THE INVENTION

[0037] The following description is of a best mode presentlycontemplated for practicing the invention. This description is not to betaken in a limiting sense but is made merely for the purpose ofdescribing the general principles of the invention. The scope of theinvention should be ascertained with reference to the issued claims. Inthe description of the invention that follows, like numerals orreference designators will be used to refer to like parts or elementsthroughout.

[0038] The present invention relates to a cardiac stimulation devicecapable of delivering precisely ordered stimulation pulses to multiplechambers of the heart, referred to herein as multi-chamber stimulation,or to multiple sites within a chamber of the heart, referred to hereinas multi-site stimulation. As used herein, the shape of the stimulationpulses is not limited to an exact square or rectangular shape, but mayassume any one of a plurality of shapes which is adequate for thedelivery of an energy packet or stimulus.

[0039] The stimulation device is intended for use in patients sufferingfrom hemodynamic dysfunction, which may or may not be accompanied byconduction disorders. Precisely controlled stimulation at multiple sitesor in multiple chambers is provided to intentionally make use of thepacing function of the heart in order to improve cardiac hemodynamics byre-coordinating heart chamber contractions and/or preventingarrhythmogenic depolarizations from occurring. Thus, the cardiacstimulation device is capable of delivering at least low-voltagestimulation pulses to multiple stimulation sites for providing pacingtherapy, and may include high-voltage stimulation shocks for providingcardioversion therapy and defibrillation therapy.

[0040]FIG. 1 illustrates a stimulation device 10 in electricalcommunication with a patient's heart 12 by way of three leads 20, 24 and30 suitable for delivering multi-chamber stimulation and shock therapy.To sense right atrial cardiac signals and to provide right atrialchamber stimulation therapy, the stimulation device 10 is coupled to animplantable right atrial lead 20 having at least an atrial tip electrode22, which typically is implanted in the patient's right atrialappendage.

[0041] To sense left atrial and/or left ventricular cardiac signals andto provide left-chamber pacing therapy, the stimulation device 10 iscoupled to a “coronary sinus” lead 24 designed for placement in the“coronary sinus region” via the coronary sinus os so as to place adistal electrode adjacent to the left ventricle and additionalelectrode(s) adjacent to the left atrium. As used herein, the phrase“coronary sinus region” refers to the vasculature of the left ventricle,including any portion of the coronary sinus, great cardiac vein, leftmarginal vein, left posterior ventricular vein, middle cardiac vein,and/or small cardiac vein or any other cardiac vein accessible by thecoronary sinus. It could also be an epicardial lead placed at the timeof thoracotomy or thorascopy.

[0042] Accordingly, the coronary sinus lead 24 is designed to receiveatrial and/or ventricular cardiac signals and to deliver: leftventricular pacing therapy using at least a left ventricular tipelectrode 26, left atrial pacing therapy using at least a left atrialring electrode 27, and shocking therapy using at least a left atrialcoil electrode 28. For a more detailed description of a coronary sinuslead, refer to U.S. patent application Ser. No. 09/196,898, titled “ASelf-Anchoring Coronary Sinus Lead” (Pianca et. al), and U.S. Pat. No.5,466,254, titled “Coronary Sinus Lead with Atrial Sensing Capability”(Helland) that are incorporated herein by reference.

[0043] The stimulation device 10 is also shown in electricalcommunication with the patient's heart 12 by way of an implantable rightventricular lead 30 having, in this embodiment, a right ventricular tipelectrode 32, a right ventricular ring electrode 34, a right ventricular(RV) coil electrode 36, and an SVC coil electrode 38. Typically, theright ventricular lead 30 is transvenously inserted into the heart 12 soas to place the right ventricular tip electrode 32 in the rightventricular apex so that the RV coil electrode 36 will be positioned inthe right ventricle and the SVC coil electrode 38 will be positioned inthe superior vena cava. Accordingly, the right ventricular lead 30 iscapable of receiving cardiac signals, and delivering stimulation in theform of pacing and shock therapy to the right ventricle.

[0044]FIG. 2 illustrates a simplified block diagram of the multi-chamberimplantable stimulation device 10, which is capable of treating bothfast and slow arrhythmias with stimulation therapy, includingcardioversion, defibrillation, and pacing stimulation. While aparticular multi-chamber device is shown, this is for illustrationpurposes only, and one of skill in the art could readily duplicate,eliminate or disable the appropriate circuitry in any desiredcombination to provide a device capable of treating the appropriatechamber(s) with cardioversion, defibrillation and/or pacing stimulation.

[0045] The stimulation device 10 includes a housing 40 which is oftenreferred to as “can”, “case” or “case electrode”, and which may beprogrammably selected to act as the return electrode for all “unipolar”modes. The housing 40 may further be used as a return electrode alone orin combination with one or more coil electrodes 28, 36, or 38, forshocking purposes. The housing 40 further includes a connector having aplurality of terminals, 42, 44, 46, 48, 52, 54, 56, and 58 (shownschematically and, for convenience, the names of the electrodes to whichthey are connected are shown next to the terminals). In accordance withthe present invention, the connector will provide a unique connectionport for each lead in communication with the heart so as to avoid thenecessity of adapters. Furthermore, the connector will provide a uniqueterminal for electrical connection to each electrode(s) associated witheach stimulation site within the heart 12. In this way, coupling of morethan one stimulation site using adaptors, or hardwiring betweenterminals inside the connector, is avoided allowing independentstimulation and sensing at each stimulation site.

[0046] As such, in the embodiment of FIG. 2, the connector includes atleast a right atrial tip terminal 42 adapted for connection to theatrial (A_(R)) tip electrode 22 in order to achieve right atrial sensingand pacing.

[0047] To achieve left chamber sensing, pacing and/or shocking, theconnector includes at least a left ventricular (V_(L)) tip terminal 44,a left atrial (A_(L)) ring terminal 46, and a left ventricular (V_(L))shocking terminal (coil) 48, which are adapted for connection to theleft ventricular tip electrode 26, the left atrial ring electrode 27,and the left atrial coil electrode 28, respectively.

[0048] To support right ventricular sensing, pacing and/or shocking, theconnector further includes a right ventricular (V_(R)) tip terminal 52,a right ventricular (V_(R)) ring terminal 54, a right ventricular (RV)shocking terminal (coil) 56, and an SVC shocking terminal (coil) 58,which are adapted for connection to the right ventricular tip electrode32, right ventricular ring electrode 34, the RV coil electrode 36, andthe SVC coil electrode 38, respectively. Thus, the embodiment of FIG. Iincludes one connection port for the right atrial lead 20 and twobipolar, high-voltage connection ports for the right ventricular lead 30and the coronary sinus lead 24, allowing sensing and stimulation in allfour chambers of the heart.

[0049] In alternative embodiments, the stimulation device 10 may includea multi-port connector capable of accommodating any combination ofthree, four or more uni-polar, bi-polar or multi-polar leads. Thearrangement and type of leads used may vary depending on the type ofstimulation therapy to be delivered and individual patient need. In apreferred embodiment, to be described later in conjunction with FIG. 3,four bipolar connection ports are provided to accommodate a programmableselection of unipolar, bipolar or combination stimulation and sensing inany or all four chambers of the heart, or at four sites within the heart12.

[0050] At the core of the stimulation device 10 is a programmablemicrocontroller 60 that controls the various modes of stimulationtherapy. As is well known in the art, the microcontroller 60 typicallyincludes a microprocessor, or equivalent control circuitry, designedspecifically for controlling the delivery of stimulation therapy, andmay further include RAM or ROM memory, logic and timing circuitry, statemachine circuitry, and I/O circuitry. Typically, the microcontroller 60includes the ability to process or monitor input signals (data) ascontrolled by a program code stored in a designated block of memory. Thedetails of the design and operation of the microcontroller 60 are notcritical to the present invention. Rather, any suitable microcontroller60 may be used that carries out the functions described herein. The useof microprocessor-based control circuits for performing timing and dataanalysis functions are well known in the art.

[0051] As shown in FIG. 2, an atrial pulse generator 70 and aventricular pulse generator 72 generate pacing stimulation pulses fordelivery by the right atrial lead 20, the right ventricular lead 30and/or the coronary sinus lead 24, via the switch bank 74. It isunderstood that in order to provide stimulation therapy in each of thefour chambers of the heart, or at multiple sites within one or morechambers, the atrial pulse generator 70 and the ventricular pulsegenerator 72 include dedicated, independent pulse generators,multiplexed pulse generators, or shared pulse generators. However, inorder to provide independent stimulation at each stimulation site,atrial pulse generator 70 and ventricular pulse generator 72 includeindependent output circuits for each stimulation site that allowdelivery of unique stimulation pulses to each site.

[0052] The atrial pulse generator 70 in FIG. 2 thus includes a rightatrial output circuit for delivering stimulation pulses to the rightatrium via right atrial lead 20, and further includes a left atrialoutput circuit for delivering stimulation pulses to the left atrium viacoronary sinus lead 24. The ventricular pulse generator 72 includes aright ventricular output circuit for delivering stimulation pulses tothe right ventricle via right ventricular lead 30, and further includesa left ventricular output circuit for delivering stimulation pulses tothe left ventricle via the coronary sinus lead 24. The atrial pulsegenerator 70 and the ventricular pulse generator 72 are controlled bythe microcontroller 60 via appropriate control signals 76 and 78,respectively, to trigger or inhibit the stimulation pulses.

[0053] The microcontroller 60 further includes timing control circuitry79 which is used to control the timing of such stimulation pulses (e.g.pacing rate, atrio-ventricular (AV) delay, interatrial conduction (A-A)delay, or interventricular conduction (V-V) delay, etc.), as well as tokeep track of the timing of refractory periods, PVARP intervals, noisedetection windows, evoked response windows, alert intervals, markerchannel timing, etc.

[0054] In accordance with one embodiment of the present invention, thetiming control circuitry 79 is also used to control coupling intervals,which precisely control the stimulation sequence during multi-chamber ormulti-site stimulation. For example, the interatrial conduction (A-A)delay may be determined by programmable selection of coupling intervalsdefined according to whether an intrinsic atrial depolarization is firstsensed in the right atrium or in the left atrium. A right-to-left atrialcoupling interval may be programmed to control the time between a rightatrial detected event (P-wave) and the delivery of a left atrialstimulation pulse. A different left-to-right atrial coupling intervalmay be programmed to control the time between a left atrial detectedP-wave and right atrial stimulation pulse delivery.

[0055] Furthermore, different coupling intervals may be defined inrelation to paced events than detected events. Hence, the couplinginterval between a right atrial paced event and a left atrial pacedevent may be different than the coupling interval between a right atrialdetected event (intrinsic P-wave) and a left atrial paced event. Inother words, for each stimulation site, a unique coupling intervalbetween it and all other stimulation sites may be defined in relation toboth paced events and detected events occurring at that site. Detailsregarding the application of coupling intervals as provided by thepresent invention will be described later in conjunction with FIGS. 5through 10.

[0056] The switch bank 74 includes a plurality of switches forconnecting the desired electrodes to the appropriate I/O circuits,thereby providing complete electrode programmability. Accordingly, theswitch bank 74, in response to a control signal 80 from themicrocontroller 60, determines the polarity of the stimulation pulses(e.g. unipolar, bipolar, combined manner, etc.) by selectively closingthe appropriate combination of switches (not shown).

[0057] In addition to providing programmable stimulation polarity, thestimulation device 10 includes the programmable polar assignments ofeach electrode during bipolar or unipolar stimulation. For example,bi-ventricular stimulation may be provided in a combined manner betweenthe right ventricular tip electrode 32 and left ventricular tipelectrode 26 by connecting these two tip electrodes to ventricular pulsegenerator 72 via switch bank 74.

[0058] The stimulation device 10 provides the programmable assignment ofcathode and anode poles in the following stimulation configuration. Theleft ventricular tip electrode 26 may be selected as the cathode withthe right ventricular tip electrode 32 selected as the anode, to achieveone directionality and stimulation threshold. Alternatively, the leftventricular tip electrode 26 may be selected as the anode and the rightventricular tip electrode 32 may be selected as the cathode, to achievea different directionality and stimulation threshold. In this way, theselection of cathode and anode assignments during bi-atrial orbi-ventricle stimulation, or within a chamber during multisitestimulation, may be tailored to meet the individual patient's need.

[0059] In some patients it may be advantageous to provide anodalstimulation rather than cathodal stimulation. Hence, it is one featureof the present invention to further allow assignment of the activeelectrode used in unipolar stimulation to be the anode with the housing40 assigned as the cathode. For example, unipolar anodal stimulation ofthe right ventricle may be achieved by designating the right ventricularring electrode 54 as the anode and the housing 40 as the cathode.

[0060] The programmable designation of electrode poles is preferablyaccomplished via electronic switching devices controlled by logic gatesreceiving high or low signals under the control of microprocessor 60.For details regarding a switching circuitry that may be used forproviding programmable selection of stimulation and sensing electrodeconfigurations, refer to U.S. Pat. No. 4,991,583 to Silvian, herebyincorporated herein by reference.

[0061] Atrial sensing circuit 82 and ventricular sensing circuit 84 mayalso be selectively coupled to the right atrial lead 20, coronary sinuslead 24, and the right ventricular lead 30, through the switch bank 74,for detecting the presence of cardiac activity in each of the fourchambers of the heart. In order to detect events occurring within eachchamber or at each stimulation site independently, the atrial andventricular sensing circuits 82 and 84 include dedicated independentsense amplifiers associated with each stimulation site within the heart12. As used herein, each of the atrial sensing circuit 82 and theventricular sensing circuit 84 includes a discriminator, which is acircuit that senses and can indicate or discriminate the origin of acardiac signal in each of the cardiac chambers.

[0062] The inputs to each sense amplifier are programmable and may beselected in any combination of available electrode terminals in order toprovide independent unipolar or bipolar sensing at each stimulationsite. In this way, a detected atrial event may be distinguished as beinga right atrial event or a left atrial event. Likewise, a detectedventricular event may be distinguished as a right ventricular event or aleft ventricular event.

[0063] If the stimulation device 10 is being used for multisitestimulation within a chamber of the heart, one electrode might bepositioned in the upper area of the chamber and a second electrode mightbe positioned in a lower area of the same chamber or any two distinctlocations within that chamber. Unique sensing circuitry for eachelectrode allows discrimination of a detected event as occurring ineither the upper area or the lower area of the chamber. The stimulationresponse provided by the device 10 may then be determined based on thelocation of a detected event.

[0064] Additionally, combination sensing for bi-atrial or bi-ventricularsensing during multichamber stimulation or combipolar sensing within asingle chamber during multisite stimulation may be selected byprogramming the appropriate inputs to the individual sense amplifiers.The switch bank 74 determines the “sensing polarity” of the cardiacsignal by selectively closing the appropriate switches. In this way, theclinician may program the sensing polarity independent of thestimulation polarity.

[0065] Each of the atrial sensing circuit 82 or the ventricular sensingcircuit 84 preferably employs one or more low power, precisionamplifiers with programmable gain and/or automatic gain control,bandpass filtering, and a threshold detection circuit, to selectivelysense the cardiac signal of interest. The automatic gain control enablesthe stimulation device 10 to deal effectively with the difficult problemof sensing the low amplitude signal characteristics of atrial orventricular fibrillation. The outputs of the atrial and ventricularsensing circuits 82 and 84 are connected to the microcontroller 60 fortriggering or inhibiting the atrial and ventricular pulse generators 70and 72, respectively, in a demand fashion, in response to the absence orpresence of cardiac activity, respectively, in the appropriate chambersof the heart.

[0066] One feature of the present invention is to provide precisecontrol of the activation sequence of the stimulation sites. To thisend, the stimulation device 10 may act only in a trigger mode therebygaining complete control of the heart rhythm in an attempt to provide amore hemodynamically effective contraction sequence of the heartchambers than that produced by the natural heart rhythm.

[0067] Preferably, the stimulation device 10 operates in a trigger modein controlling the timing of contraction at all the stimulation sites.Alternatively, it may operate in a demand mode in delivering orinhibiting stimulation pulses to at least one site, and may operate in atrigger mode in delivering stimulation pulses to all other stimulationsites. For example, atrial pulse generator 70 may be inhibited fromdelivering a right atrial stimulation pulse when atrial sensing circuit82 detects an intrinsic P-wave in the right atrium within a given escapeinterval. However, this detection may cause microcontroller 60 totrigger atrial pulse generator 70 and ventricular pulse generator 72 todeliver stimulation pulses at prescribed intervals of time to the leftatrium and the right and left ventricles, respectively, regardless ofany events detected in these chambers. In this way, the activationsequence of all four heart chambers is precisely controlled by thenatural pacemaking activity of the sinus node. Hence, in the presentinvention, the pacing mode of stimulation device 10, that is demand ortrigger mode, for each stimulation site is preferably programmable.

[0068] If the cardiac stimulation device 10 is also intended fordelivering cardioversion and defibrillation therapy, arrhythmiadetection by the stimulation device 10 utilizes the atrial andventricular sensing circuits 82 and 84 to sense cardiac signals, fordetermining whether a rhythm is physiologic or pathologic. As usedherein “sensing” is reserved for the noting of an electrical signal, and“detection” is the processing of these sensed signals and noting thepresence of an arrhythmia. The timing intervals between sensed events(e.g. P-waves, R-waves, and depolarization signals associated withfibrillation which are sometimes referred to as “F-waves” or“Fib-waves”) are then classified by the microcontroller 60 by comparingthem to a predefined rate zone limit (e.g. bradycardia, normal, low rateVT, high rate VT, and fibrillation rate zones) and various othercharacteristics (e.g. sudden onset, stability, physiologic sensors, andmorphology, etc.) in order to determine the type of remedial therapythat is needed (e.g. bradycardia pacing, anti-tachycardia pacing,cardioversion shocks or defibrillation shocks, collectively referred toas “tiered therapy”).

[0069] Cardiac signals are also applied to the inputs of ananalog-to-digital (A/D) data acquisition system 90. The data acquisitionsystem 90 is configured to acquire intracardiac electrogram (EGM)signals, convert the raw analog data into digital signals, and store thedigital signals for later processing and/or telemetric transmission toan external device 102. The data acquisition system 90 is coupled to theright atrial lead 20, the coronary sinus lead 24, and the rightventricular lead 30 through the switch bank 74 to sample cardiac signalsacross any pair of desired electrodes.

[0070] The microcontroller 60 is further coupled to a memory 94 by asuitable data/address bus 96, wherein the programmable operatingparameters used by the microcontroller 60 are stored and modified, asrequired, in order to customize the operation of the stimulation device10 to suit the needs of a particular patient. Such operating parametersdefine, for example, pacing pulse amplitude, pulse duration, electrodepolarity, rate, sensitivity, automatic features, arrhythmia detectioncriteria, and the amplitude, wave shape and vector of each shockingpulse to be delivered to the patient's heart 12 within each respectivetier of therapy.

[0071] Advantageously, the operating parameters of the stimulationdevice 10 may be non-invasively programmed into the memory 94 through atelemetry circuit 100 in telemetric communication with the externaldevice 102, such as a programmer, transtelephonic transceiver, or adiagnostic system analyzer. The telemetry circuit 100 is activated bythe microcontroller 60 by a control signal 106. The telemetry circuit100 advantageously allows intracardiac electrograms and statusinformation relating to the operation of the stimulation device 10 (ascontained in the microcontroller 60 or memory 94) to be sent to theexternal device 102 through the established communication link 104.

[0072] The stimulation device 10 may further include a physiologicsensor 108, commonly referred to as a “rate-responsive” sensor becauseit is typically used to adjust pacing stimulation rate according to theexercise state of the patient. However, the physiological sensor 108 mayfurther be used to detect changes in cardiac output, changes in thephysiological condition of the heart, or diurnal changes in activity(e.g. detecting sleep and wake states). Accordingly, the microcontroller60 responds by adjusting the various pacing parameters (such as rate, AVDelay, V-V Delay, etc.) at which the atrial and ventricular pulsegenerators 70 and 72 generate stimulation pulses.

[0073] In accordance with one feature of the present invention, couplingintervals that determine the activation sequence of stimulated chambersor sites, may be adjusted based on changes detected by the physiologicsensor 108. Preferably physiologic sensor 108 includes detection ofchanges related to the hemodynamic state of the patient and therebyallows adjustment of the coupling intervals to be made in a way thatoptimizes the hemodynamic response to multisite or multichamberstimulation. One method for accomplishing automatic adjustment ofcoupling intervals based on physiologic sensor 108 data will bedescribed in detail in conjunction with FIG. 10.

[0074] While the physiologic sensor 108 is shown as being includedwithin the stimulation device 10, it is to be understood that thephysiologic sensor 108 may alternatively be external to the stimulationdevice 10, yet still be implanted within, or carried by the patient. Acommon type of rate responsive sensor is an activity sensor, such as anaccelerometer or a piezoelectric crystal, which is mounted within thehousing 40 of the stimulation device 10. Other types of physiologicsensors are also known, for example, sensors which sense the oxygencontent of blood, cardiac output, respiration rate and/or minuteventilation, pH of blood, ventricular gradient, etc. However, any sensormay be used which is capable of sensing a physiological parameter, whichcorresponds to the exercise or hemodynamic state of the patient.

[0075] The stimulation device 10 additionally includes a power sourcesuch as a battery 110 that provides operating power to all the circuitsshown in FIG. 2. For the stimulation device 10, which employs shockingtherapy, the battery 110 must be capable of operating at low currentdrains for long periods of time, and also be capable of providinghigh-current pulses (for capacitor charging) when the patient requires ashock pulse. The battery 110 must preferably have a predictabledischarge characteristic so that elective replacement time can bedetected. Accordingly, the stimulation device 10 can employ, forexample, lithium/silver vanadium oxide batteries.

[0076] As further shown in FIG. 2, the stimulation device 10 is shown ashaving an impedance measuring circuit 112 which is enabled by themicrocontroller 60 by a control signal 114. The known uses for animpedance measuring circuit 120 include, but are not limited to, leadimpedance surveillance during the acute and chronic phases for assessingthe mechanical integrity of the lead; detecting operable electrodes andautomatically switching to an operable pair if mechanical disruptionoccurs in one lead; measuring respiration or minute ventilation;detecting when the device has been implanted; and a variety ofhemodynamic variables such as measuring stroke volume; and detecting theopening of the valves, etc. The impedance measuring circuit 120 isadvantageously coupled to the switch bank 74 so that any desiredelectrode may be used.

[0077] The impedance measuring circuit 112 may be used advantageously inthe present invention for monitoring hemodynamic indicators, such asventricular impedance as an indication of cardiac output, to providefeedback in the selection of optimal coupling intervals. Impedancemeasuring circuit 112 may be used alone or in conjunction withphysiological sensor 108 for providing such feedback. This data may beperiodically stored in memory 94 such that a physician may then accessthis data during patient follow-up visits to obtain useful informationin manually selecting and programming coupling intervals. Preferably,this data may be used by the stimulation device 10 to automaticallyadjust coupling intervals as will be described in conjunction with FIG.10.

[0078] In cases where a primary function of the stimulation device 10 isto operate as an implantable cardioverter/defibrillator (ICD) device, itmust detect the occurrence of an arrhythmia, and automatically apply anappropriate antitachycardia pacing (ATP) and/or electrical shock therapyto the heart aimed at terminating the detected arrhythmia. To this end,the microcontroller 60 further controls a shocking circuit 116 by way ofa control signal 118. The shocking circuit 116 generates shocking pulsesof low (up to 0.5 Joules), moderate (0.5-10 Joules), or high (11 to 40Joules) energy, as controlled by the microcontroller 60. Such shockingpulses are applied to the patient's heart through at least two shockingelectrodes, and as shown in this embodiment, selected from the leftatrial coil electrode 28, the RV coil electrode 36, and/or the SVC coilelectrode 38 (FIG. 1). As noted earlier, the housing 40 may act as anactive electrode in combination with the RV electrode 36, or as part ofa split electrical vector using the SVC coil electrode 38 or the leftatrial coil electrode 28 (i.e., using the RV electrode as commonelectrode).

[0079] Cardioversion shocks are generally considered to be of low tomoderate energy level (so as to minimize pain felt by the patient),and/or synchronized with an R-wave and/or pertaining to the treatment oftachycardia. Defibrillation shocks are generally of moderate to highenergy level (i.e., corresponding to thresholds in the range of 5-40Joules), delivered asychronously (since R-waves may be toodisorganized), and pertaining exclusively to the treatment offibrillation. Accordingly, the microcontroller 60 is capable ofcontrolling the synchronous or asynchronous delivery of the shockingpulses.

[0080]FIG. 3 illustrates a preferred embodiment of the present inventionshowing one bipolar lead 20 implanted in the right atrium, one bipolarlead 21 implanted in the coronary sinus region adjacent to left atrium,one bipolar high-voltage lead 30 implanted in the right ventricle, andanother bipolar high-voltage lead 31 implanted in the coronary sinusregion adjacent to the left ventricle. Using this electrodeconfiguration with the stimulation device 10, independent unipolar orbipolar stimulation and sensing of either or both atria is possible, or,alternatively, combination bi-atrial stimulation or sensing can beperformed with the cathode and anode assignments applied to the rightatrial tip electrode 22, right atrial ring electrode 23, left atrialring electrode 27, and left atrial tip electrode 29 as desired.

[0081] In addition, independent unipolar or bipolar stimulation andsensing can be provided separately in the right and left ventricles or,alternatively, combination bi-ventricular stimulation or sensing can beperformed with the cathode and anode assignments applied to the rightventricular tip electrode 32, right ventricular ring electrode 34, leftventricular ring electrode 25, and left ventricular tip electrode 26 asdesired.

[0082] In this embodiment, and as further illustrated in FIG. 4, thestimulation device 10 of FIG. 3 includes four bipolar connection ports200, 210, 220 and 230. A left ventricular connection port (LV connectionport) 200 accommodates the left ventricular lead (LV lead) 24 withterminals 44, 45, 48 that are associated with the left ventricular tipelectrode (LV tip electrode) 26, the left ventricular ring electrode (LVring electrode) 25, and the left atrial coil electrode (LA coilelectrode) 28, respectively.

[0083] A left atrial connection port (LA connection port) 210accommodates the left atrial lead (LA lead) 21 with terminals 49, 47that are associated with the left atrial tip electrode (LA tipelectrode) 29 and the left atrial ring electrode (LA ring electrode) 27,respectively. A right ventricular connection port (RV connection port)220 accommodates the right ventricular lead (RV lead) 30 with terminals52, 54, 56, 58 that are associated with the right ventricular tipelectrode (RV tip electrode) 32, the right ventricular ring electrode(RV ring electrode) 34, the right ventricular coil electrode (RVCE) 36and the right ventricular SVC coil electrode (RV SVC coil electrode) 38,respectively. A right atrial connection port (RA connection port) 230accommodates the right atrial lead (RA lead) 20 with terminals that areassociated with the right atrial tip electrode (RA tip electrode) 22 andthe right atrial ring electrode (RA ring electrode) 23, respectively.

[0084] It is recognized that numerous variations exist in whichcombinations of unipolar, bipolar and/or multipolar leads may bepositioned at desired locations within the heart in order to providemultichamber or multisite stimulation. The present invention providesfor the flexibility of independent stimulation and/or sensing atmultiple sites by providing a cardiac stimulation device that includesmultiple connection ports with unique terminals for the electrode(s)associated with each stimulation site as well as independent sensing andoutput circuitry for each stimulation site. As such, stimulation andsensing sites are not obligatorily coupled together by adapters orhardwiring within the stimulation device that would otherwise precludeindependent sensing and stimulation at each pacing site during eithermultichamber or multisite pacing.

[0085]FIGS. 5 and 6 illustrate a flow chart describing methods ofoperation 200 and 300, respectively, that are implemented in oneembodiment of the stimulation device 10 in which defined couplingintervals are applied by microcontroller 60 for controlling the sequenceof stimulation pulse delivery by the atrial pulse generator 70 and theventricular pulse generator 72. In this flow chart, and the other flowcharts described herein, the various algorithmic steps are summarized inindividual “blocks”. Such blocks describe specific actions or decisionsthat must be made or carried out as the algorithm proceeds. Where amicrocontroller (or equivalent) is employed, the flow charts presentedherein provide the basis for a “control program” that may be used bysuch a microcontroller (or equivalent) to effectuate the desired controlof the stimulation device. Those skilled in the art may readily writesuch a control program based on the flow charts and other descriptionspresented herein.

[0086] The methods 200 and 300 will be described in relation to theimplant configuration of FIG. 3, where sensing and pacing are performedin the right atrium, left atrium, right ventricle and left ventricle. Itis recognized that the algorithmic steps illustrated in FIGS. 5 and 6may easily be modified to control the stimulation sequence during anymultichamber or multi-site stimulation configuration.

[0087] At the time of implant, coupling intervals are programmed by thephysician to precisely control the activation sequence of all fourchambers whenever pacing is required. Default nominal values stored inthe stimulation device 10 may also be selected. Coupling intervals aredefined in association with paced and sensed events occurring at eachstimulation site. For example, the delivery of a right atrialstimulation pulse by the atrial pulse generator 70 will causemicrocontroller 60 to initiate three coupling intervals: one associatedwith the left atrium; another associated with the right ventricle; andyet another associated with the left ventricle. These coupling intervalscontrol the time between the delivery of the right atrial stimulationpulse and the delivery of the left atrial, right ventricular, and leftventricular stimulation pulses, respectively.

[0088] Likewise, the detection of a P-wave in the right atrium by theatrial sense circuitry 82 will also cause microcontroller 60 to initiatethree coupling intervals associated with the left atrium, rightventricle, and left ventricle. However, these coupling intervals may bedifferent than the coupling intervals initiated due to a right atrialpaced event. Similarly, left atrial coupling intervals are defined forthe case of a left atrial event being detected before a right atrialevent for controlling the time between the left atrial detection andright atrial stimulation, right ventricular stimulation and leftventricular stimulation. In addition, the system can be configured todeliver the left atrial stimulus before the right atrial stimulus, orthe left ventricular stimulus before the right ventricular stimulus.

[0089] The method 200 and 300 of FIGS. 5 and 6 represent the applicationof these coupling intervals over one cardiac cycle. It is assumed inthis example, that the stimulation device 10 is programmed to operate ina demand mode in the atrial channels and in a triggered mode in theventricular channels although, it can be set to operate in the triggeredmode in both the atrium and ventricle or the triggered mode in theatrium and the demand mode in the ventricle.

[0090] Starting at step 202, a new escape interval is initiated. Thelength of this escape interval is determined by the programmed basepacing (or stimulation) rate. For example, if the base pacing rate isprogrammed to be 60 beats per minute, then the escape interval is 1000msec. Method 200 waits for the detection of an intrinsic P-wave byatrial sense circuit 82 prior to expiration of the escape interval.

[0091] If at decision step 204 the method 200 determines that the escapeinterval has expired before an intrinsic P-wave is detected,microprocessor 60 triggers the right atrial output circuitry in theatrial pulse generator 70 to deliver a stimulation pulse to the rightatrium at step 206, according to the programmed electrode configurationfor stimulation in the right atrium.

[0092] The delivery of a right atrial stimulation pulse causesmicroprocessor 60 to trigger timing control circuitry 79 to start threeseparate timers simultaneously at step 208. As it is illustrated in FIG.7, one timer initiates a right atrial pace to left atrium (RApace to LA)coupling interval at step 325. Another timer initiates a right atrialpace to right ventricle (RApace to RV) coupling interval at step 335.The third timer simultaneously initiates a right atrial pace to leftventricle (RApace to LV) coupling interval at step 345. Upon expirationof the coupling intervals, the stimulation device 10 delivers therequired stimulation pulses at step 310.

[0093]FIG. 7 illustrates further details of step 310. Upon expiration ofthe right atrial pace to left atrium (RApace to LA) coupling interval(step 325), method 300 inquires, at decision step 326, if an intrinsicleft atrial depolarization (P-wave) is detected. If it is, method 300inhibits the delivery of a left atrial stimulation pulse at step 328. Ifan intrinsic left atrial depolarization is not detection at step 326,the microcontroller 60 triggers the left atrial output circuitry ofatrial pulse generator 70 to deliver a left atrial (LA) stimulationpulse at step 327.

[0094] Similarly, upon expiration of the right atrial pace to leftatrium (RApace to RV) coupling interval at step 335, method 300inquires, at decision step 336, if an intrinsic right ventriculardepolarization (R-wave) is detected. If it is, method 300 inhibits thedelivery of a right ventricular stimulation pulse at step 338. If anintrinsic right ventricular depolarization is not detection at step 336,the microcontroller 60 triggers the right atrial output circuitry of theventricular pulse generator 72 to deliver a right ventricular (RV)stimulation pulse at step 337.

[0095] In a similar manner, upon expiration of the right atrial pace toleft ventricle (RApace to LV) coupling interval at step 345, method 300inquires, at decision step 346, if an intrinsic left ventriculardepolarization (R-wave) is detected. If it is, method 300 inhibits thedelivery of a left ventricular stimulation pulse at step 348. If anintrinsic left ventricular depolarization is not detected at step 346,the microprocessor 60 triggers the left atrial output circuitry of theventricular pulse generator 72 to deliver a left ventricular (LV)stimulation pulse at step 347.

[0096] With respect to steps 328, 338, and 348, if a sensed event occurson the atrial channel or the ventricular channel, method 300 detects thechamber in which the sensed event originated and the times the deliveryof the output pulse to the other chamber in accord with the automatic orphysician set interval.

[0097] After the expiration of all these three coupling intervals andthe delivery of triggered stimulation to the designated stimulationsites, method 300 returns to step 202 where the microprocessor 60initiates a new escape interval to start the next cardiac pacing cycle.

[0098] Returning now to FIGS. 5 and 6, if a P-wave is detected by theatrial sense circuitry 82 prior to the expiration of the escape intervalat decision step 204, methods 200 and 300 determine, at decision step216, if this detection has been made by the right atrial sensingcircuitry or the left atrial sensing circuitry of the atrial sensecircuit 82.

[0099] If a P-wave is detected at step 204 and the microprocessor 60determines that the P-wave has been detected in the left atrial sensecircuitry of atrial sense circuitry 82 at decision step 216, then thecoupling intervals associated with a left atrial sense event areinitiated by timing the control circuitry 79 at step 217. As it isillustrated in FIG. 8, a left atrial sense to right atrial (LAsense toRA) coupling interval is initiated in one timer at step 425. Thiscoupling interval may or may not be equal to the coupling intervalbetween the right and left atria associated with a detected right atrialevent.

[0100] On a separate timer, the timing control circuitry 79simultaneously initiates a left atrial sense to right ventricle (LAsenseto RV) coupling interval at step 435. Another timer starts the leftatrial sense to left ventricle (LAsense to LV) coupling interval at step445. If a sensed event occurs within the designated coupling intervals,the timing of the stimulus output to the other chamber is based on thesensed event and not the output pulse in the atrium. Upon expiration ofthe coupling intervals, the stimulation device 10 delivers the requiredstimulation pulses at step 318.

[0101]FIG. 8 illustrates further details of step 318. Upon expiration ofthe left atrial sense to right atrial (LAsense to RA) coupling intervalat step 425, method 300 inquires, at decision step 426, if an intrinsicright atrial depolarization (P-wave) is detected. If it is, method 300inhibits the delivery of a right atrial stimulation pulse at step 428.If an intrinsic left atrial depolarization is not detection at step 426,the microprocessor 60 triggers the right atrial output circuitry of theatrial pulse generator 70 to deliver a stimulation pulse to the rightatrium at step 427.

[0102] Similarly, upon expiration of the left atrial to rightventricular (LAsense to RV) coupling interval at step 435, method 300inquires, at decision step 436, if an intrinsic right ventriculardepolarization (R-wave) is detected. If it is, method 300 inhibits thedelivery of a right ventricular stimulation pulse at step 438. If anintrinsic right ventricular depolarization is not detection at step 436,the microcontroller 60 triggers right ventricular output circuitry ofthe ventricular pulse generator 72 to deliver a stimulation pulse to theright ventricle at step 437.

[0103] In a similar manner, upon expiration of the left atrial to leftventricular (LAsense to LV) coupling interval at step 445, method 300inquires, at decision step 446, if an intrinsic left ventriculardepolarization (R-wave) is detected. If it is, method 300 inhibits thedelivery of a left ventricular stimulation pulse at step 348. If anintrinsic left ventricular depolarization is not detection at step 446,the microprocessor 60 triggers the left ventricular output circuit ofthe ventricular pulse generator 72 to deliver a stimulation pulse to theleft ventricle at step 447.

[0104] Returning now to FIGS. 5 and 6, if the P-wave detection has beenmade in the right atrium, the microprocessor 60 commands the timingcontrol circuitry 79 to simultaneously initiate three different timersat step 220. As it is illustrated in FIG. 9, one timer starts the rightatrial sense to left atrium (RAsense to LA) coupling interval (step455). Another timer simultaneously starts the right atrial sense toright ventricle (RAsense to RV) coupling interval (step 465). The thirdtimer starts the right atrial sense to left ventricle (RAsense to LV)coupling interval (step 475). These coupling intervals triggered by aright atrial sense event may be different than the coupling intervalstriggered by a right atrial pace event as described above in conjunctionwith steps 425, 435, and 445. Upon expiration of the coupling intervals,the stimulation device 10 delivers the required stimulation pulses atstep 322.

[0105]FIG. 9 illustrates further details of step 322. Upon expiration ofthe right atrial sense to left atrium (RAsense to LA) coupling intervalat step 455, method 300 inquires, at decision step 456, if an intrinsicright atrial depolarization (P-wave) is detected. If it is, method 300inhibits the delivery of a left atrial stimulation pulse at step 457. Ifan intrinsic left atrial depolarization is not detection at step 456,the microprocessor 60 triggers the left atrial output circuitry of theatrial pulse generator 70 to deliver a left atrial (LA) stimulationpulse at step 457.

[0106] Similarly, upon expiration of the right atrial pace to rightventricular (RApace to RV) coupling interval at step 465, method 300inquires, at decision step 466, if an intrinsic right ventriculardepolarization (R-wave) is detected. If it is, method 300 inhibits thedelivery of a right ventricular stimulation pulse at step 468. If anintrinsic right ventricular depolarization is not detection at step 436,the microcontroller 60 triggers the ventricular pulse generator 72 todeliver a right ventricular (RV) stimulation pulse at step 467.

[0107] In a similar manner, upon expiration of the right atrial sense toleft ventricular (RAsense to LV) coupling interval at step 475, method300 inquires, at decision step 476, if an intrinsic left ventriculardepolarization (R-wave) is detected. If it is, method 300 inhibits thedelivery of a left ventricular stimulation pulse at step 478. If anintrinsic left ventricular depolarization is not detection at step 476,the microprocessor 60 triggers the left atrial output circuitry of theventricular pulse generator 72 to deliver a left ventricular (LV)stimulation pulse. After the expiration of these three couplingintervals and the delivery of triggered stimulation to the designatedstimulation sites, method 300 returns to step 202 (FIG. 6) where themicroprocessor 60 initiates a new escape interval to start the nextcardiac cycle.

[0108] In this way, the sequential delivery of stimulation pulses to allfour chambers of the heart is precisely controlled in order to providecoordinated depolarization of the cardiac chambers. In this example, thestimulation device 10 essentially operates in a demand pacing mode inthe right and left atria and in a triggered pacing mode in the right andleft ventricles, though other possibilities are similarly feasible, asdescribed herein. Sensing within all of these chambers is stillprovided, however, in order to accommodate the tachycardia detectionfeatures of the stimulation device 10, and to utilize its ability todeliver shocking therapy in addition to pacing therapy as needed.

[0109] The programmed settings of the coupling intervals described inconjunction with FIG. 5 are preferably selected in a way that providesoptimal hemodynamic benefit to the patient. A medical practitioner maymanually program these settings based on clinical measurements ofcardiac performance. It is recognized that the selection and programmingof numerous coupling intervals associated with numerous stimulationsites could become a time-consuming task. Therefore, the selection ofcoupling intervals may be semi-automatic or completely automatic. Forexample, after manual programming of the most critical couplingintervals, the microprocessor 60 might calculate other couplingintervals based on mathematical relationships or patient's historystored in memory 90, or apply default values to other couplingintervals.

[0110] In an alternative embodiment of the present invention, theoptimal coupling intervals may be selected automatically based onmeasurements of cardiac function or other physiological parameters thatrelate to the clinical condition of the patient as measured byphysiological sensor 108 and/or impedance measuring circuit 112.

[0111]FIG. 10 illustrates a method 500 for automatically adjusting thecoupling intervals. The method 500 may be performed upon delivery of anexternal command, or on a programmed periodic basis, for example, daily.Method 500 starts at step 505 by verifying that the patient is at rest.Preferably, physiological measurements made for comparing cardiac stateduring different pacing modalities is performed only at rest in order toavoid confounding variables that may occur if the patient is engaged invarying levels of activity during the test. Various methods may be usedto verify resting state, such as heart rate or other physiologicalsensor 108 measured parameters. For details regarding one method forverifying resting state reference is made to U.S. Pat. No. 5,476,483 toBornzin.

[0112] At step 510, the microprocessor 60 determines the present pacingstate of the stimulation device 10. If the device 10 is programmed to beoperating in a demand mode in both the atrial and ventricular chambers,it may be in one of four pacing states: atrial pacing and ventricularpacing (AV pacing state), atrial pacing and ventricular sensing (ARpacing state), atrial sensing and ventricular pacing (PV pacing state)or atrial sensing and ventricular sensing (PR pacing state).

[0113] If the stimulation device 10 is pacing in the ventricle, that isin either the AV or PV pacing states, an attempt is made to inhibitventricular pacing by extending the atrial-ventricular (AV) delay toallow more time for an intrinsic R-wave to occur at step 515. If thestimulation device 10 is pacing in the atrium, that is in either the AVor AR pacing states, an attempt is made to inhibit atrial pacing byreducing the base pacing rate in order to allow the natural heart rateto predominate at step 520.

[0114] Preferably, all pacing is inhibited in order to obtain a baselinephysiologic measurement during the natural resting state of the heart.If ventricular pacing cannot be inhibited, even at the maximum AV delaysetting, such as in the situation of total AV block, no further attemptis made to inhibit ventricular pacing. Atrial pacing may also not beinhibited even at a minimum pacing rate due to sinus node dysfunctionwith either too slow a native sinus rate or an unstable native sinusrate. In such cases, the minimum base pacing rate and a nominal AV delayare applied.

[0115] At step 525, a measurement is made using the physiological sensor108 and/or impedance measurement circuit 112 to establish a baselinecardiac function. At step 530, the coupling intervals are modulated in away that allows testing of numerous combinations of coupling intervals,thus altering the activation sequence, in order to determine theactivation sequence and timing that allows optimal improvement incardiac state. Initially, coupling intervals between the atria andcoupling intervals between the ventricles may be modulated. Next, the AVdelay, herein referred to as the atrial to ventricular couplingintervals, may be modulated. Pacing should be sustained for any givenset of “test” coupling intervals for a defined minimum time period, suchas one minute, to allow the functional state of the heart to stabilizeunder the “test” conditions before making physiological measurements atstep 535.

[0116] Preferably, the stimulation device 10 operates in a trigger modethroughout this test in order to provide a steady cardiac rhythm at eachset of coupling intervals. The physiological measurement made by thesensor 108 and/or the impedance measurement made by impedance measuringcircuit 112 are stored in memory 94 (FIG. 2) with codes indicating thecorresponding coupling interval settings at step 540.

[0117] The coupling interval settings resulting in the greatestimprovement in cardiac function based on sensor 108 measurements and/orimpedance circuit 112 measurements are selected as the final settings.At step 545, the optimal coupling interval settings are automaticallyre-programmed. The physiologic sensor 108 measurement and/or theimpedance measuring circuit 112 measurement at these final settingsshould be stored in histogram memory 94 to be recalled and displayedgraphically over time during patient follow-up visits.

[0118] Thus, a multichamber or multisite cardiac stimulation device hasbeen provided which allows independent sensing and stimulation atmultiple sites within the heart according to programmed electrodeconfigurations. Furthermore, a method by which the activation sequenceof the stimulated sites may be precisely controlled using programmablecoupling intervals has been provided. Thus, greater flexibility insensing and stimulation during multisite or multichamber stimulationtherapies may be achieved whereby pacing therapies may be individuallytailored to patient need so that optimal hemodynamic orelectrophysiological results may be realized.

[0119] While detailed descriptions of specific embodiments of thepresent invention have been provided, it would be apparent to thosereasonably skilled in the art that numerous variations of multi-site ormulti-chamber stimulation configurations are possible in which theconcepts and methods of the present invention may readily be applied.The descriptions provided herein, therefore, are for the sake ofillustration and are no way intended to be limiting.

What is claimed is:
 1. A method of automatically controlling anactivation sequence of a plurality of electrodes that are positioned inmultiple cardiac chambers, for use with a multi-site cardiac stimulationdevice, the method comprising the steps of: defining a plurality ofelectrode configurations corresponding to available activation sequencesof the electrodes; selectively delivering a stimulus, on demand, to acardiac chamber; sensing a cardiac event in the cardiac chamber by usinga first electrode configuration; initiating a coupling interval for themultiple cardiac chambers; controlling the activation sequence of theelectrodes by selecting an electrode configuration based on the cardiacchamber in which the cardiac event is sensed or a stimulus delivered;automatically acquiring a measurement of the cardiac event using theelectrode configuration; and automatically adjusting the couplinginterval in response to the measurement of the cardiac event.
 2. Themethod according to claim 1, wherein the sensing step includes sensingintrinsic depolarizations in at least two cardiac chambers.
 3. Themethod according to claim 2, wherein the step of delivering a stimulusincludes stimulating at least two cardiac chambers.
 4. The methodaccording to claim 3, further including the step of determining aninter-atrial conduction (A-A) delay by selecting a coupling intervaldefined according to whether an intrinsic atrial depolarization is firstsensed in a right atrium or in a left atrium.
 5. The method according toclaim 4, wherein the step of automatically adjusting includes selectinga right-to-left atrial coupling interval to control an interval betweenan intrinsic right atrial depolarization (P-wave) and a delivery of aleft atrial stimulus.
 6. The method according to claim 4, wherein thestep of automatically adjusting includes selecting a left-to-rightatrial coupling interval to control an interval between an intrinsicleft atrial depolarization (P-wave) and a delivery of a right atrialstimulus.
 7. The method according to claim 1, wherein the step ofautomatically adjusting further includes adjusting the coupling intervalbased on a stimulation event in any one of the multiple cardiacchambers.
 8. The method according to claim 1, wherein the step ofinitiating a coupling interval includes initiating a unique couplinginterval for a stimulation site, between the stimulation site andremaining stimulation sites, in terms of any one or more of: astimulations event or an intrinsic depolarization occurring at thestimulation site.
 9. The method according to claim 1, further includingsensing an occurrence of an intrinsic atrial depolarization in any oneor more of a left atrium or a right atrium.
 10. The method according toclaim 9, further including delivering a right atrial stimulation pulsewhen no intrinsic atrial depolarization is sensed.
 11. The methodaccording to claim 10, wherein the step of initiating the couplinginterval includes initiating one or more coupling intervals from theright atrial stimulation pulse to any one or more of: a left atrialstimulation pulse, a right ventricular stimulation pulse, or a leftventricular stimulation pulse.
 12. The method according to claim 10,further including detecting an occurrence of an intrinsic right atrialdepolarization.
 13. The method according to claim 12, wherein when theintrinsic right atrial depolarization is not sensed, initiating one ormore coupling intervals from the intrinsic right atrial depolarizationto any one or more of: a left atrial stimulation pulse, a rightventricular stimulation pulse, or a left ventricular stimulation pulse.14. The method according to claim 13, wherein when an intrinsic leftatrial depolarization is sensed, initiating one or more couplingintervals from the intrinsic left atrial depolarization to any one ormore of: a right atrial stimulation pulse, a right ventricularstimulation pulse, or a left ventricular stimulation pulse.
 15. Themethod according to claim 1, further including automatically selecting asensing polarity for each sensing site in the multiple cardiac chambers.16. The method according to claim 15, wherein the step of automaticallyselecting the sensing polarity includes designating any of an anode or acathode assignment to at least one of the plurality of sensingelectrodes.
 17. The method according to claim 16, wherein the step ofdesignating includes selecting a left ventricular tip electrode as thecathode, and further selecting a right ventricular tip electrode as theanode.
 18. The method according to claim 16, wherein the step ofdesignating includes selecting a right ventricular tip electrode as thecathode, and further selecting a left ventricular tip electrode as theanode.
 19. The method according to claim 16, wherein the step ofdesignating includes assigning any of an anodal sensing or a cathodalsensing to at least one of the plurality of sensing electrodes.
 20. Themethod according to claim 16, wherein the step of designating includesassigning any of an anodal sensing or a cathodal sensing to at least oneof the plurality of sensing electrodes.
 21. The method according toclaim 16, further including automatically selecting a stimulationpolarity for each stimulation site in the multiple cardiac chambers. 22.The method according to claim 21, wherein the step of automaticallyselecting the stimulation polarity includes designating any of an anodeor a cathode assignment to at least one of a plurality of stimulationelectrodes.
 23. The method according to claim 22, wherein the step ofdesignating includes selecting a left ventricular tip electrode as thecathode, and further selecting a right ventricular tip electrode as theanode.
 24. The method according to claim 22, wherein the step ofdesignating includes selecting a right ventricular tip electrode as thecathode, and further selecting a left ventricular tip electrode as theanode.
 25. The method according to claim 22, wherein the step ofdesignating includes assigning any of an anodal sensing or a cathodalsensing to at least one of the plurality of sensing electrodes.
 26. Themethod according to claim 1, further including allowing intrinsicdepolarizations occurring at each stimulation site to be sensedindependently.
 27. The method according to claim 1, wherein the step ofautomatically adjusting the coupling interval includes determining acurrent stimulation state of the stimulation device; when thestimulation device is stimulating a ventricle, attempting to inhibitventricular stimulation by extending an atrial-ventricular (AV) delay;when the stimulation device is stimulating an atrium, attempting toinhibit atrial pacing by reducing a base pacing rate; measuring one ormore baseline physiological parameters; and modulating one or morecombinations of the coupling intervals for altering the activationsequence so as to determine an activation sequence that allows optimalimprovement in the current stimulation state.
 28. A multi-site cardiacstimulation device capable of automatically controlling an activationsequence of a plurality of electrodes that are positioned in multiplecardiac chambers, comprising: a discriminator, coupled to the pluralityof electrodes, that senses a cardiac signal in each of the cardiacchambers, and that identifies a cardiac chamber of origin in which thecardiac signal originates; a pulse generator, connected to theelectrodes, to selectively deliver stimulation pulses on demand to thecardiac chambers; and timing control circuitry, connected to theelectrodes, the pulse generator, and the discriminator to initiatecoupling intervals for the multiple cardiac chambers based on thecardiac chamber of origin in which an intrinsic depolarization is sensedor a stimulus is delivered, for controlling a timing of the activationsequence, and the timing control circuitry further automaticallyadjusting the coupling intervals based on measurements acquired by thediscriminator.
 29. The stimulation device according to claim 28, whereinthe discriminator senses an occurrence of an intrinsic atrialdepolarization in any one or more of a left atrium or a right atrium.30. The stimulation device according to claim 29, wherein the pulsegenerator delivers a right atrial stimulation pulse in the absence of anintrinsic atrial depolarization.
 31. The stimulation device according toclaim 29, wherein the timing control circuitry initiates one or morecoupling intervals from a right atrial stimulation pulse to any one ormore of: a left atrial stimulation pulse, a right ventricularstimulation pulse, or a left ventricular stimulation pulse.
 32. Thestimulation device according to claim 29, wherein the sensing circuitryis adapted to further sense an occurrence of an intrinsic right atrialdepolarization; and wherein in the absence of an intrinsic right atrialdepolarization, the timing control circuitry initiates one or morecoupling intervals from the intrinsic right atrial depolarization to anyone or more of: a left atrial stimulation pulse, a right ventricularstimulation pulse, or a left ventricular stimulation pulse.
 33. Thestimulation device according to claim 29, wherein in the presence of anintrinsic left atrial depolarization, the sensing circuitry initiatesone or more coupling intervals from the intrinsic left atrialdepolarization to any one or more of: a right atrial stimulation pulse,a right ventricular stimulation pulse, or a left ventricular stimulationpulse.
 34. The stimulation device according to claim 28, wherein theplurality of electrodes include sensing electrodes; and furtherincluding a switch bank that automatically selects polarities for theplurality of sensing electrodes.
 35. The stimulation device according toclaim 30, wherein the plurality of electrodes include stimulationelectrodes; and further including a switch bank that automaticallyselects polarities for the plurality of stimulation electrodes.
 36. Thestimulation device according to claim 30, further including a multi-portconnector for connection to any one or more of uni-polar, bi-polar, ormulti-polar leads.
 37. The stimulation device according to claim 36,wherein the multi-port connector includes four bipolar connection ports:a left ventricular connection port that couples to a left ventricularlead with terminals associated with a ventricular tip electrode, a leftventricular ring electrode, and a left atrial coil electrode; a leftatrial connection port that couples to a left atrial lead with terminalsassociated with a left atrial tip electrode and a left atrial ringelectrode; a right ventricular connection port that couples to a rightventricular lead with terminals associated with a right ventricular tipelectrode, a right ventricular ring electrode, a right ventricularshocking coil, and a right ventricular coil electrode; and a rightatrial connection port that couples to a right atrial lead withterminals associated with a right atrial tip electrode and a rightatrial ring electrode.
 38. A multi-site cardiac stimulation devicecapable of automatically controlling an activation sequence of aplurality of electrodes that are positioned in multiple cardiacchambers, comprising: means for sensing a cardiac signal in each of themultiple cardiac chambers; means for detecting a cardiac chamber oforigin in which the cardiac signal originates; means for selectivelygenerating stimulation energy, on demand, to the multiple cardiacchambers; and means for initiating coupling intervals for the multiplecardiac chambers based on the cardiac chamber of origin in which anintrinsic depolarization is sensed or a stimulus is delivered, forcontrolling a timing of the activation sequence, and for automaticallyadjusting the coupling intervals based on measurements acquired by thesensing means.
 39. The stimulation device according to claim 38, whereinthe sensing means senses an occurrence of an intrinsic atrialdepolarization in any one or more of a left atrium or a right atrium.40. The stimulation device according to claim 39, wherein the means forgenerating stimulation energy delivers a right atrial stimulation pulsein the absence of an intrinsic atrial depolarization; wherein theinitiating means initiates one or more coupling intervals from a rightatrial stimulation pulse to any one or more of: a left atrialstimulation pulse, a right ventricular stimulation pulse, or a leftventricular stimulation pulse; wherein in the absence of an intrinsicright atrial depolarization, the initiating means initiates one or morecoupling intervals from the intrinsic right atrial depolarization to anyone or more of: a left atrial stimulation pulse, a right ventricularstimulation pulse, or a left ventricular stimulation pulse; and whereinin the presence of an intrinsic left atrial depolarization, theinitiating means initiates one or more coupling intervals from theintrinsic left atrial depolarization to any one or more of: a rightatrial stimulation pulse, a right ventricular stimulation pulse, or aleft ventricular stimulation pulse.
 41. The stimulation device accordingto claim 38, wherein the plurality of electrodes include sensingelectrodes; and further including switching means for automaticallyselecting polarities for the plurality of sensing electrodes.
 42. Thestimulation device according to claim 38, wherein the plurality ofelectrodes include stimulation electrodes; and further includingswitching means for automatically selecting polarities for the pluralityof stimulation electrodes.
 43. The stimulation device according to claim38, further including a multi-port connecting means for connection toany one or more of uni-polar, bi-polar, or multi-polar leads; andwherein the multi-port connecting means includes four bipolar connectionports: a left ventricular connection port that couples to a leftventricular lead with terminals associated with a ventricular tipelectrode, a left ventricular ring electrode, and a left atrial coilelectrode; a left atrial connection port that couples to a left atriallead with terminals associated with a left atrial tip electrode and aleft atrial ring electrode; a right ventricular connection port thatcouples to a right ventricular lead with terminals associated with aright ventricular tip electrode, a right ventricular ring electrode, aright ventricular shocking coil, and a right ventricular coil electrode;and a right atrial connection port that couples to a right atrial leadwith terminals associated with a right atrial tip electrode and a rightatrial ring electrode.